Blocking serotonin receptors has been shown to result in a number of beneficial pharmacological effects, including reduction in disease states such as hypertension, depression, anxiety, and the like; see U.S. Pat. No. 5,141,944. Nelson et al., Psychopharmacology and Biochemistry of Neurotransmitter Receptors, eds. H. I. Yamamura et al., Elsevier/North Holland Inc., p 325, have confirmed that there are multiple serotonin recognition sites. The general class of serotonin receptors are referred to as the 5-HT receptors. Specific 5-HT receptor sites include 5-HT.sub.1A, 5-HT.sub.1B, 5-HT.sub.1D, 5-HT.sub.2A, 5-HT.sub.2B, 5-HT.sub.2C, 5-HT.sub.3, and 5-HT.sub.4 sites. Each of these receptors mediates certain physiological effects. See Leonard, B. E., International Clinical Psychopharmacology, 7:13-21 (1992).
This invention provides new compounds and a method for using such compounds which are active at the 5-HT.sub.2B receptor to treat or prevent 5-HT.sub.2B related conditions. Further, this invention provides a method for selectively blocking the 5-HT.sub.2B receptor. Additionally, this invention provides a method for blocking human 5-HT.sub.2B receptors.
This invention provides a group of compounds which are 5HT.sub.2B receptor antagonists. Applicants have discovered that such compounds are potent competitive inhibitors of serotonin-induced contraction of the colon. Thus, this invention provides compounds which can act to normalize gastrointestinal motility and be useful in the treatment of Functional Bowel Disorders.
Further, it has been discovered the 5-HT.sub.2B receptor is localized in the rat lung, stomach fundus, uterus, bladder, and colon. Interesting areas of 5-HT.sub.2B receptor localization in the human include but are not limited to the brain and blood vessels. Thus, conditions which can be treated using a compound which modulates a B-HT.sub.2B receptor includes, for example, psychosis, depression, anxiety disorders, uterine diseases such as endometriosis, fibrosis, and other abnormal uterine contractivity, panic attack, migraine, eating disorders, seasonal affective disorder, consumption disorders, cardiovascular conditions, such as thrombosis, hypertension, angina, vasospasm, and other vascular occlusive diseases, incontinence, bladder dysfunction, respiratory/airway disorders including asthma, and the like.